A device for the extraction and detection of biological macromolecules

Abstract

The present application discloses a device for the extraction and detection of biological macromolecules. The device of the present application comprises a reaction cartridge assembly and a detection system; the reaction cartridge assembly includes a number of sector-shaped reaction units that can form a disc shape, and each reaction unit is provided with a first functional area, a second functional area, and a third functional area. The first functional area includes a cavity for sample injection, the second functional area includes a cavity for sample extraction and purification, and the third functional area includes a cavity for reaction detection; the first functional area is internally connected to the second functional area, and the second functional area is internally connected to the third functional area; the detection system is used to control the reaction cartridge assembly to perform extraction and detection. For the device of the present application, after the sample to be tested enters from the first functional area, the extraction and detection reactions are both carried out in a relatively independent and enclosed reaction unit, which simplifies the entire detection process and better avoids cross-contamination between samples at the same time. The combination of multiple reaction units can improve the detection throughput.

Description

Technical Field

[0001] This application relates to the field of biomacromolecule detection devices, and particularly to a device for extracting and detecting biomacromolecules. Background Art

[0002] Nucleic acid is a biomacromolecule polymerized by many nucleotides and is one of the most basic substances of life, widely existing in all plants, animals, and microorganisms. Molecular diagnostic techniques based on nucleic acid detection are commonly used detection methods in modern biomedicine. Diagnosis is made by detecting the results and changes in the expression levels of exogenous and autologous genetic materials in patients using molecular biological methods, which have the characteristics of good specificity, high sensitivity, no "window period", and rapid diagnosis. Currently, molecular diagnosis based on nucleic acid detection is the fastest-growing technical field in clinical laboratory applications. However, factors such as the large volume of equipment required for nucleic acid detection, complex operation processes, high personnel requirements, risks of contamination and infection, and the need to be completed in a laboratory with clearly defined partitions have greatly restricted its clinical promotion and application.

[0003] The nucleic acid detection process includes steps such as sample processing, nucleic acid purification, detection, and result analysis. There are already relatively mature products on the market for automated equipment for individual steps, but there are still high requirements and many restrictions on laboratory space, detection time, and the skills of operators. At the same time, it is also impossible to avoid sample - to - sample or aerosol contamination and the risk of sample infection to laboratory personnel.

[0004] Currently, there are a few integrated devices and equipment for nucleic acid purification and testing, such as GeneXpert Ststem, Biofire Filmarry, etc., which can achieve nucleic acid detection within a closed detection device. However, there are still deficiencies such as complex fixed - design structures, high prices, commonly used for qualitative detection, and a small number of detected samples. At the same time, there is a disadvantage that after sample collection, the sample needs to be manually transferred to the detection device, which poses a risk of infection to operators by high - risk samples. Consumables such as pipette tips after sample transfer are externally processed, which may cause environmental pollution and increase the risk of medical waste treatment. Generally speaking, existing devices and equipment such as GeneXpert Ststem, Biofire Filmarry, etc. have the following defects and deficiencies:

[0005] 1) Complex fixed - design structure: The detection items, reactions, and operations involved in the extraction and detection processes have different requirements for the production and manufacturing of nucleic acid extraction and purification devices. Different types of detected samples may require significantly different pretreatment methods. The fixed - design has great limitations in terms of the types of detected samples, and at the same time, the complex structure increases the requirements for samples.

[0006] 2) Expensive: The complex device structure, material requirements, and assembly of fragmented components all increase the overall cost of the device and the assembly cost, resulting in an expensive overall product price.

[0007] 3) Commonly used for qualitative detection: Existing devices mostly adopt microchannel and chip designs, and the driving methods are mostly pneumatic or external pushing, etc. There are disadvantages such as incomplete liquid transfer and small liquid transfer volume, resulting in a large error in the overall sample volume in the reaction detection area, leading to problems such as poor precision and insufficient sensitivity, and it is not easy to achieve quantitative detection with high sensitivity, high accuracy, and high precision requirements.

[0008] 4) Small number of detected samples: This type of detection device generally adopts a multi-chamber and microchannel design, and there are problems such as a relatively large device volume and a large number of external driving devices. Therefore, the instrument cannot achieve simultaneous detection of multiple sample volumes. If multiple sample detections are required, it can only be achieved by connecting multiple instruments in parallel or in series.

[0009] 5) Risk of manual sample transfer after collection: Currently, this type of device is equipped with sample tubes or sample chambers, and it is necessary to manually transfer an accurate volume of the sample to the corresponding cavity of the device. When operating on highly infectious pathogens such as Ebola virus and influenza virus, there is an infection risk to the inspection operators, and it is required to be carried out in corresponding safety equipment such as a biosafety cabinet. Therefore, the existing devices have certain limitations and safety hazards in use, and at the same time, the precise sample addition volume requires the inspection personnel to have a relatively high skill level.

[0010] 6) Risk of consumables after sample transfer: After the sample is transferred to the detection device, the discarded consumables have certain infectivity and infection risk.

[0011] In addition, Roche COBAS series devices, Tianlong Technology PANA9600E, Daan DA3200, etc. adopt a combination of robotic arms and magnetic bead purification to achieve semi-automation of semi-closed detection. Although to a certain extent, they achieve simultaneous inspection of multiple samples and quantitative detection, due to semi-closed detection, there are still disadvantages such as cross-contamination between samples, manual sample transfer, high consumable costs, and long inspection time. Therefore, devices and equipment such as Roche COBAS series devices, Tianlong Technology PANA9600E, and Daan DA3200 have the following defects and deficiencies:

[0012] 1) Cross - contamination between samples: The robotic arm sucks samples through specific tips and then transfers and extracts them, leaving the samples in a semi - open state during the purification and detection process. During the transfer process by the robotic arm, situations such as aerosol generation and liquid droplet dripping are likely to occur, leading to cross - contamination between samples. Conventionally, ultraviolet inactivation is used to treat aerosols after a single detection, but ultraviolet light cannot completely remove pollutants. Therefore, in addition to the risk of cross - contamination in the current detection, there is also a risk of pollutant accumulation.

[0013] 2) Manual sample transfer: The problem of manual sample transfer cannot be solved. For example, samples such as blood, urine, and saliva need to be collected and then manually transferred into matching sample tubes, and then operations such as sample loading are carried out by instruments. Although the sample volume problem can be solved, there are still problems such as the risk of infection and contamination, equipment requirements, and requirements for personnel's technical level.

[0014] 3) High consumable costs: The detection requires various supporting consumables, such as pipette tips, purification consumables, detection reaction consumables, cleaning solutions, etc. The types and quantities of consumables are relatively large, resulting in high costs.

[0015] 4) Long testing time: Limited by the operating speed and quantity of the robotic arm, multiple samples cannot be detected simultaneously. Therefore, during the detection process, a one - by - one detection method is adopted. When multiple samples are detected simultaneously, the detection time is proportional to the number of detected samples.

[0016] Hormones and proteins are another type of biological macromolecule substances expressed directly or indirectly by nucleic acids and are important components of all cells and tissues in the human body. The device for the integrated purification and detection of hormones and proteins also has similar problems to nucleic acid detection, such as sample cross - contamination, manual sample transfer, high consumable costs, long testing time, etc.

[0017] Therefore, with the research and development of biological macromolecule detection, there is an urgent need to develop a new integrated device or equipment that is more convenient to use and can solve a series of problems such as cross - contamination between samples, the risk of infection for testing operators, small throughput of detected samples, and environmental protection and safety of consumables. Summary of the Invention

[0018] The purpose of this application is to provide a new device for the extraction and detection of biological macromolecules.

[0019] This application adopts the following technical solutions:

[0020] The present application discloses a device for the extraction and detection of biological macromolecules, wherein the biological macromolecules are hormones, proteins or nucleic acids. The device of the present application includes a reaction cartridge assembly and a detection system; the reaction cartridge assembly includes a plurality of sector-shaped reaction units, and all the reaction units are assembled into a disc-shaped reaction cartridge. Each reaction unit is used to independently extract and detect the biological macromolecules in the sample to be tested; a first functional area, a second functional area and a third functional area are provided on each reaction unit. The first functional area includes a cavity for sample injection, the second functional area includes a cavity for extraction and purification, and the third functional area includes a cavity for reaction detection; a part of the cavity in the first functional area is internally connected to a part of the cavity in the second functional area, or a part of the cavity in the first functional area is respectively internally connected to a part of the cavity in the second functional area and a part of the cavity in the third functional area; a part of the cavity in the second functional area is internally connected to the cavity for reaction detection in the third functional area; the detection system is used to control the reaction cartridge assembly to extract and detect biological macromolecules.

[0021] It should be noted that the key of the present application lies in the structural improvement of the reaction cartridge assembly. As for the detection system, reference can be made to existing nucleic acid automatic extraction and detection devices or protein automatic extraction and detection devices. It can be understood that the detection system is nothing but to realize the automatic extraction and detection of biological macromolecules through automatic sample addition, robotic arm operation and reaction, and the provision of detection conditions; in order to ensure the effective progress of extraction and detection, the detection system is specifically limited in the improved solution of the present application, and details can be seen in the following technical solutions.

[0022] For the device of the present application, the sample to be tested enters the reaction unit through the cavity for sample introduction in the first functional area, then enters the second functional area through the internal connection pipeline for extraction and purification. After obtaining the biological macromolecules, it directly enters the cavity for reaction detection in the third functional area through the internal connection pipeline for the detection of biological macromolecules. It can be understood that in the device of the present application, according to the specific type of biological macromolecules, the types and quantities of cavities can be designed in each functional area according to requirements, and different types of reagents can be pre-encapsulated to achieve corresponding functions. For example, the cavities for extraction and purification in the second functional area may include cavities for sample lysis and cavities for biological macromolecule collection. Reagents for sample lysis and fragmentation are pre-encapsulated in the cavities for sample lysis, and corresponding collection or elution reagents are pre-encapsulated in the cavities for biological macromolecule collection according to the type of biological macromolecules collected. In the third functional area, corresponding detection reagents are pre-encapsulated according to the required detection reaction. For the device of the present application, one reaction unit can achieve the detection of one or a group of samples to be tested. Moreover, the entire extraction and detection process is completed inside one reaction unit, which can not only avoid sample cross-contamination, but also, from extraction to detection, there is no need for manual operations such as transferring the extracted samples. The sample transfer is directly achieved through the internal connection pipeline of the reaction unit, making the detection safer and more environmentally friendly; truly realizing the fully automatic extraction and detection of "sample in, result out". In addition, multiple reaction units can be included in one reaction cartridge assembly of the device of the present application. Therefore, the simultaneous detection of multiple samples can be achieved, improving the sample detection throughput.

[0023] It can be understood that the cavity for sample introduction in the first functional area of the present application can be one or more cavities, and the specific quantity depends on the samples to be tested that need to be detected and analyzed. Moreover, in addition to the cavity for sample introduction, other functional cavities can be included according to requirements. For example, for some reagents that cannot be pre-mixed, the first functional area can also include cavities for storing special reagents. The quantity of such cavities depends on the quantity of special reagents that need to be stored separately. Such cavities are connected to the cavities in the corresponding second functional area and / or third functional area for delivering the stored special reagents to the designated cavities when needed. Similarly, in the second functional area of the present application, the cavities for extraction and purification can be provided with functional cavities according to different usage requirements, such as cavities for lysis and fragmentation and cavities for biological macromolecule collection, etc. The specific quantity of each functional cavity depends on the experimental design or requirements. Similarly, the third functional area is mainly for the cavities for reaction detection, and the quantity of its cavities can also be determined according to the experimental design or requirements, and no specific limitation is made here.

[0024] It should also be noted that the cavities in each functional area of the present application can be designed into circular, square or any other shape as needed. The device of the present application is developed according to the integrated extraction and detection of biological macromolecules. The key lies in that after the sample is added, the reaction cassette assembly can automatically perform extraction, purification and detection reactions inside the reaction unit. It can be understood that the device of the present application can not only be used for the integrated extraction and detection of biological macromolecules, but also for the detection of other biological samples. Only the functional cavities in each functional area need to be adjusted adaptively, and the corresponding detection system can be used. Therefore, the device of the present application is not limited to the extraction and detection of biological macromolecules.

[0025] Preferably, the second functional area is arranged at the central position of the sector-shaped reaction unit, and all the cavities in the second functional area are evenly arranged on the circumference with the central position as the center of the circle.

[0026] It should be noted that in the present application, the central position of the sector-shaped reaction unit refers to the center of gravity or the geometric center of the entire reaction unit, and the center of the circle of the sector-shaped reaction unit refers to the intersection point of the two side edges of the sector, that is, the center of the circular reaction cassette. It can be understood that the second functional area of the present application is mainly for the purification of biological macromolecules. The cavities in this area can be designed for sample lysis and biological macromolecule collection according to needs. Arranging the cavities in the second functional area on a circumference is for the convenience of extraction operations.

[0027] Preferably, the entire second functional area is arranged in a circular groove with the central position of the sector-shaped reaction unit as the center of the circle, and the circular groove is sealed by an extraction screw cap magnetic sleeve, so as to seal the second functional area in the circular groove.

[0028] It should be noted that arranging the entire second functional area in the groove is for the convenience of sealing it, separating the second functional area from other functional areas and avoiding contamination.

[0029] Preferably, at the positions corresponding to each cavity of the extraction screw cap magnetic sleeve, there are respectively provided sealing sleeves for closing each cavity, and the extraction screw cap magnetic sleeve is provided with an electromagnetic column extending into the cavity.

[0030] It should be noted that the sealing sleeve is for better sealing and isolation. In one implementation mode of the present application, the design of the electromagnetic column uses magnetic beads to adsorb biological macromolecules for extraction and purification. The electromagnetic column can adsorb magnetic beads, playing a role similar to that of a magnetic rack to adsorb and fix magnetic beads. The present application uses the electromagnetic column to adsorb magnetic beads and extract the biological macromolecules adsorbed by the magnetic beads, and sequentially passes through the functional cavities in the second functional area to realize the extraction, purification and collection of biological macromolecules.

[0031] Preferably, in the second functional area, the cavities for extraction and purification include a cavity for lysis and fragmentation and a cavity for collecting biological macromolecules.

[0032] Preferably, the second functional area further includes a cavity for rinsing.

[0033] It can be understood that for nucleic acid extraction, after the sample is lysed and fragmented, it is necessary to wash the nucleic acid to remove corresponding impurities, so a cavity for rinsing is required; for proteins and hormones, if rinsing is not required, a cavity for rinsing is not needed. Therefore, the cavity for rinsing and its quantity can be determined according to the usage design or usage requirements.

[0034] Preferably, in one implementation manner of the present application, in the second functional area, the cavity for lysis and fragmentation is at least one lysis and fragmentation cavity, the cavity for collecting biological macromolecules is at least one collection cavity, and the cavity for rinsing includes a first rinsing cavity and a second rinsing cavity; each cavity in the second functional area is independently arranged, and moreover, the cavity for sample injection in the first functional area is internally connected to the lysis and fragmentation cavity, and the cavity for reaction detection in the third functional area is internally connected to the collection cavity.

[0035] It should be noted that taking the nucleic acid extraction and detection in the embodiments of the present application as an example, the second functional area is composed of a lysis and fragmentation cavity, a first rinsing cavity, a second rinsing cavity and a collection cavity, and the four cavities can basically meet the experimental requirements for nucleic acid extraction, purification and elution.

[0036] Preferably, sealing sleeves for closing each cavity are respectively arranged at positions corresponding to the lysis and fragmentation cavity, the first rinsing cavity, the second rinsing cavity and the collection cavity of the extraction screw cap magnetic sleeve; and starting from the lysis and fragmentation cavity as the starting position, an electromagnetic column extending into the cavity is provided at the corresponding position of the extraction screw cap magnetic sleeve.

[0037] It should be noted that in one implementation of the present application, specifically, nucleic acid or protein is combined with magnetic beads, and then the nucleic acid or protein combined with the magnetic beads is adsorbed by an electromagnetic column to achieve extraction and separation; the function of the extraction screw cap magnetic sleeve is, on the one hand, to seal the entire second functional area, and on the other hand, to lift the extraction screw cap magnetic sleeve and rotate it to make the electromagnetic column correspond to different cavities to respectively achieve the functions of rinsing and elution. For example, after the lysis and fragmentation are completed and the nucleic acid or protein is adsorbed on the inserted electromagnetic column, the extraction screw cap magnetic sleeve is lifted by the robotic arm, rotated to make the electromagnetic column above the first rinsing cavity, the extraction screw cap magnetic sleeve is lowered, and the electromagnetic column is inserted into the first rinsing cavity for the first rinsing; after the first rinsing is completed, the same method is used to sequentially perform the second rinsing and elution collection. It can be understood that during the entire process of lifting and rotating the extraction screw cap magnetic sleeve, the extraction screw cap magnetic sleeve seals the second functional area. Therefore, the purpose of designing the entire second functional area in the groove is to better isolate the second functional area. Of course, it is not excluded that other methods can also be used to isolate the second functional area.

[0038] Preferably, on the back of the reaction unit, at the position corresponding to the second functional area, there is a hollow structure, so that each cavity of the second functional area forms a protruding independent tubular structure, and an oscillator can be optionally connected to the outer wall of each protruding cavity. Here, optionally connecting an oscillator means that an oscillator can be selected to be connected according to requirements, such as an ultrasonic oscillator.

[0039] It should be noted that the purpose of each cavity forming a protruding independent tubular structure is to facilitate connecting an oscillator to the outer wall, so as to facilitate sample fragmentation or reaction solution mixing.

[0040] Preferably, the communication pipelines between the first functional area and the second functional area, between the second functional area and the third functional area, the cavity for sample injection in the first functional area, the cavity for sample lysis and fragmentation in the second functional area, and the cavity for reaction detection in the third functional area are all arranged on the central axisymmetric longitudinal section of the reaction unit.

[0041] It should be noted that in this application, the axially symmetric longitudinal section refers to the longitudinal section of the sector reaction unit along the central axis. Cutting along this longitudinal section is equivalent to dividing the sector reaction unit into smaller sector structures, and the left and right sides are symmetrical. In one implementation of this application, the cavity for sample injection is one injection cavity, the cavity for sample lysis and fragmentation is one lysis and fragmentation cavity, and the cavity for reaction detection is one detection reaction cavity. The connecting pipe between the second functional area and the third functional area is the first pipe that is internally connected between the injection cavity and the lysis and fragmentation cavity, and the connecting pipe between the second functional area and the third functional area is the second pipe that is internally connected between the lysis and fragmentation cavity and the detection reaction cavity; the above-mentioned cavities and internal channels are arranged on the axially symmetric longitudinal section of the reaction unit. The first pipe is longitudinally split into two, and the same is true for the second pipe. Such a design facilitates the preparation of the first pipe and the second pipe for internal connection.

[0042] Preferably, the cavity of the first functional area is arranged on the arc of the sector reaction unit.

[0043] It should be noted that the cavity of the first functional area is arranged on the arc of the sector reaction unit, so that in the entire reaction cartridge, the cavities of the first functional areas of all reaction units are evenly arranged on the circumference of the reaction cartridge. Such a design can move the cavity of the first functional area to the corresponding robotic arm operation station by rotating the reaction cartridge disc, which is convenient for the robotic arm to operate.

[0044] Preferably, in the first functional area, the cavity for sample injection is at least one injection cavity, and the injection cavity is internally connected to the second functional area to provide the sample to be tested for the second functional area.

[0045] Preferably, the injection cavity is equipped with a matching injection cavity sealer, and the two are in an insertion-type sealing fit and are connected by threads; and, by inserting the injection cavity sealer into the injection cavity, pressure is provided for the injection cavity using the pressing principle, so that the sample to be tested therein enters the second functional area for extraction and purification.

[0046] It should be noted that for the device of this application, when not in use, the injection cavity sealer seals the injection cavity to avoid contamination; it is only opened when in use. After adding the sample, the injection cavity sealer is used to seal it again to ensure that it is not contaminated and to avoid cross-contamination of the samples; and the sample to be tested is pressed into the second functional area by squeezing the injection cavity sealer.

[0047] Preferably, the first functional area further includes a cavity for storing consumables.

[0048] Preferably, the cavity for storing consumables is at least one consumable storage cavity, and the consumable storage cavity is a tip accommodating cavity, which is equipped with a matching tip. It can be understood that according to different consumables, there can be other types of cavities, which are not specifically limited here.

[0049] It should be noted that the design of the consumable storage cavity is considered for the need of automatic sample addition. If manual addition of the sample to be tested is adopted, the consumable storage cavity is not required. However, in order to reduce the infection risk of the test operator, a consumable storage cavity is designed on the reaction unit in this application. The sample to be tested is added by means of automatic pipetting, and the used pipette tips are uniformly placed in the consumable storage cavity, avoiding the pollution of the environment by the consumables.

[0050] Preferably, the pipette tip and the pipette tip receiving cavity are in an insertion-type tight fit, and the two are fixed by screw connection; after the pipette tip is inserted into the pipette tip receiving cavity, the pipette tip is fixed in the pipette tip receiving cavity by screwing tightly.

[0051] It can be understood that the design of the screw connection is to place the pipette tip more firmly in the pipette tip receiving cavity of the consumable storage cavity. In one implementation manner of this application, a pipette tip with a specially designed threaded outer wall is provided, which is pre-installed and tightened before use to keep the pipette tip clean. After the pipette tip is used, it is tightened again, and the purpose of sealing and storing the contaminated consumables can be achieved by screwing tightly.

[0052] Preferably, the first functional area further includes a cavity for placing the sample tube.

[0053] Preferably, the cavity for placing the sample tube is at least one sample tube storage cavity for placing the sample tube containing the sample to be tested.

[0054] Preferably, the sample tube is made of a highly permeable material, the tube body contains a protruding clamping position, the upper part of the sample tube contains a thread, the sample tube has a matching tube cap, and the tube cap is threadedly connected to the sample tube and is tightened or opened by the operation of the robotic arm.

[0055] It can be understood that the purpose of the sample tube storage cavity is also to facilitate the automatic addition of the sample to be tested within the range of the reaction unit.

[0056] It should be noted that the consumable storage cavity and the sample tube storage cavity are the preferred design solutions of this application. In the existing integrated devices and equipment, usually a consumable storage area and a sample tube storage area are designed in a designated common area; while in this application, a consumable storage cavity and a sample tube storage cavity are designed in each reaction unit, making the reactions of each reaction unit relatively independent, which can not only detect more samples to be tested, but also better avoid cross-contamination between samples.

[0057] Preferably, a groove and a hollow window are provided on the arc-shaped side surface of the fan-shaped reaction unit; the hollow window is arranged at the position of the sample tube storage cavity for facilitating the observation or detection of the sample tube; the groove is arranged side by side with the hollow window for pasting corresponding information or numbers.

[0058] It should be noted that the design of the hollow window facilitates the observation or detection of the inside of the sample tube. For example, it can be used to observe whether there is enough sample in the sample tube. The design of the groove is to facilitate the pasting of information such as reaction units or sample numbers, so as to intuitively observe which sample the reaction unit specifically corresponds to, or it can be used to paste QR codes or barcodes to facilitate the automatic scanning and reading of relevant information.

[0059] Preferably, the cavity of the third functional area is arranged at the included angle of the fan-shaped reaction units; moreover, in the disc-shaped reaction box, the cavities for reaction detection of all reaction units are evenly distributed on the circumference of the center of the fan-shaped reaction units.

[0060] It should be noted that the purpose of arranging the cavity of the third functional area at the included angle of the fan-shaped reaction units is to enable the cavities for reaction detection of all reaction units in the reaction box to be relatively concentrated near the center, which can facilitate the control of reaction conditions or the collection of detection signals for the cavities for reaction detection.

[0061] Preferably, in the third functional area, the cavity for reaction detection is at least one detection reaction cavity, and the detection reaction cavity is internally connected to the second functional area for receiving the biological macromolecules extracted and purified by the second functional area.

[0062] Preferably, the detection reaction cavity is of a tubular structure or a columnar cavity. The lower part of the detection reaction cavity is a transparent and smooth reaction area for placing detection reaction reagents, and the upper part of the detection reaction cavity is sealed by a matching reaction cavity seal.

[0063] Preferably, the reaction cavity seal is in an insertion-type sealing fit with the detection reaction cavity and is connected by a thread; when the reaction cavity seal is inserted into the detection reaction cavity to seal it, the opening connecting the detection reaction cavity to the second functional area is also closed.

[0064] It should be noted that since the detection reaction cavity is in a sealed state, a negative pressure will be formed when the reaction cavity seal is withdrawn, thereby sucking the biological macromolecules obtained in the second functional area, such as the biological macromolecules in the collection cavity, into the detection reaction cavity, mixing them with the corresponding detection reaction reagents, and then covering the reaction cavity seal for subsequent reactions.

[0065] It should also be noted that the reaction chamber seal is threadedly connected to the detection reaction chamber to better achieve sealing. Moreover, before the reaction, the reaction chamber seal is designed to close the opening communicating with the second functional area, aiming to prevent the elution solution from entering the reaction area before the biomacromolecules are eluted, resulting in false negatives. In principle, without opening the reaction chamber seal, the eluent will not automatically enter the reaction area, and closing the opening is also to avoid accidents. In addition, in the reaction unit of the present application, the solution with biomacromolecules is sucked into the reaction area by the negative pressure driven when the reaction chamber seal is opened. It can be understood that under the closed-opening design, the tubular structure cavity can be pre-designed to a certain negative pressure state or vacuum state, so as to provide a greater pressure difference and make the eluent in the collection chamber be sucked into the detection reaction chamber more completely and quickly.

[0066] Preferably, in the device of the present application, the detection system includes a reaction cassette assembly support, a robotic arm, and a reaction detection module. The reaction cassette assembly support includes a vertical support body and a reaction cassette assembly driving device. The support body is used to support the entire reaction cassette assembly in the vertical or horizontal direction, and the reaction cassette assembly driving device is used to drive the reaction cassette assembly to move up and down or horizontally. The reaction detection module is arranged directly below the reaction cassette assembly, and a cavity matching the cavity for reaction detection in the third functional area is provided on the reaction detection module, which is used to provide corresponding reaction and detection conditions for the reaction detection cavity. The robotic arm is closely arranged beside the reaction cassette assembly and is used for sample addition and performing clamping, up-and-down movement, and rotation operations.

[0067] In the device of the present application, the function of the support body is to support the reaction cassette assembly to facilitate its up-and-down or horizontal movement. In addition to adopting the structure of the support body, it is not excluded that other structures capable of effectively supporting the reaction cassette assembly can also be used.

[0068] Preferably, in the device of the present application, the detection system further includes an information reading module for detecting and reading the information of the sample and the reaction unit.

[0069] It can be understood that in the reaction cassette assembly of the present application, each reaction unit can be numbered and information recorded. These numbers and information records can be designed at the blank positions of the units according to requirements. The information reading module can automatically identify and read the numbers and information records of the reaction units to facilitate experiment management.

[0070] Preferably, in the device of the present application, the reaction cartridge assembly further includes a disc-shaped reaction unit tray and a tray holder; the tray holder is a frame structure that surrounds the circumference of the reaction unit tray, and the tray holder is movably connected to the reaction cartridge assembly bracket to mount the reaction cartridge assembly on the reaction cartridge assembly bracket; the reaction unit tray is rotatably arranged in the tray holder and is driven to rotate by a corresponding driving device; several cavities matching the reaction units are arranged on the surface of the reaction unit tray for mounting the reaction units, and a through-hole structure is provided at the center of the reaction unit tray, and the cavity of the third functional area of the reaction unit for reaction detection extends out of the through-hole and inserts into the cavity of the reaction detection module for reaction and detection.

[0071] It should be noted that the design of the reaction unit tray and the tray holder is to facilitate the movement of the reaction cartridge assembly. Among them, the reaction unit tray is disc-shaped. In one implementation manner of the present application, the basic position of the robotic arm is relatively fixed. By rotating the reaction unit tray, the reaction units are moved one by one to the working position of the robotic arm for operations such as sample addition. Therefore, a disc-shaped reaction unit tray is designed; it can be understood that if other methods are adopted, such as not fixing the working position of the robotic arm, the reaction unit tray may not be needed or its rotation may not be required. The design of the tray holder is to connect with the reaction cartridge assembly bracket and facilitate the up and down movement of the reaction cartridge assembly.

[0072] It can be understood that in the device of the present application, for nucleic acid detection, the reaction detection module can refer to existing conventional PCR devices or real-time fluorescence PCR devices, and for protein detection, it can refer to existing protein detection and analysis systems. For real-time fluorescence PCR, the thermal reaction module of the present application can not only provide thermal cycling reaction conditions, but also design a fluorescence collection component with reference to existing real-time fluorescence PCR devices and connect it to the user terminal in an existing connection manner to achieve real-time fluorescence PCR and view the real-time fluorescence PCR results on the user terminal. The device of the present application truly realizes the full-automatic detection of "sample in, result out". In the device of the present application, the extraction and detection processes of the entire sample to be tested are carried out in one reaction unit, solving the problem of sample cross-contamination; moreover, the reaction cartridge assembly is composed of several reaction units, and multiple reaction units can be used according to the number of samples to be tested, enabling the simultaneous detection of multiple samples, which is simple and convenient to use and has a high throughput.

[0073] The beneficial effects of the present application are as follows:

[0074] In the device of the present application, after the sample to be tested enters the reaction unit from the first functional area, the extraction and detection reactions of biological macromolecules are carried out in a relatively independent and enclosed reaction unit, simplifying the entire detection process. Moreover, in the preferred embodiment, the second functional area for extraction and the third functional area for detection are respectively enclosed, which can better avoid cross-contamination between samples. The device of the present application can detect multiple samples simultaneously, improving the detection throughput of the integrated device and equipment for the extraction and detection of biological macromolecules. Description of the Drawings

[0075] Figure 1 is a schematic diagram of the internal structure of the nucleic acid extraction and detection device in the embodiment of the present application;

[0076] Figure 2 is a schematic diagram of a partial structure of the thermal reaction module of the nucleic acid extraction and detection device in the embodiment of the present application;

[0077] Figure 3 is a schematic diagram of a partial structure of the reaction cartridge assembly of the nucleic acid extraction and detection device in the embodiment of the present application;

[0078] Figure 4 is a schematic diagram of a partially enlarged structure of the reaction cartridge assembly of the nucleic acid extraction and detection device in the embodiment of the present application;

[0079] Figure 5 is a schematic diagram of the internal structure of the reaction cartridge assembly of the nucleic acid extraction and detection device in the embodiment of the present application;

[0080] Figure 6 is a schematic diagram of the structure of the reaction unit tray in the embodiment of the present application;

[0081] Figure 7 is a schematic diagram of the structure of the tray rack in the embodiment of the present application;

[0082] Figure 8 is a schematic diagram of the assembled structure of the reaction unit tray and the tray rack in the embodiment of the present application;

[0083] Figure 9 is a schematic diagram of the structure of the reaction unit in the embodiment of the present application;

[0084] Figure 10 is a three-dimensional schematic diagram of the reaction unit in the embodiment of the present application;

[0085] Figure 11 is an exploded schematic diagram of the reaction unit in the embodiment of the present application;

[0086] Figure 12 is an exploded schematic diagram of the reaction unit from another perspective in the embodiment of the present application;

[0087] Figure 13 It is a schematic three-dimensional structure diagram of the internal cross-section of the reaction unit in the embodiment of the present application;

[0088] Figure 14 It is an internal cross-sectional view of the reaction unit in the embodiment of the present application;

[0089] Figure 15 It is a schematic diagram of the back structure of the reaction unit in the embodiment of the present application;

[0090] Figure 16 It is a schematic three-dimensional structure diagram of the extraction screw cap magnetic sleeve in the embodiment of the present application;

[0091] Figure 17 It is a schematic diagram of the structure of the extraction screw cap magnetic sleeve from another perspective in the embodiment of the present application. Detailed implementation manners

[0092] The present application will be further described in detail below through specific embodiments. The following embodiments are only for further illustration of the present application and should not be construed as limitations on the present application.

[0093] Embodiment

[0094] This example provides a device for nucleic acid extraction and detection, as Figures 1 to 5 shown, including a reaction cartridge assembly 1 and a detection system. Among them, the detection system includes a reaction cartridge assembly bracket 2, a robotic arm 3, and a thermal reaction module 4.

[0095] The reaction cartridge assembly in this example, as Figures 6 to 9 shown, includes a plurality of fan-shaped reaction units 11, a disk-shaped reaction unit tray 12, and a tray bracket 13. All the reaction units in this example are assembled into a disk-shaped reaction cartridge, and each reaction unit 11 is used to independently extract and detect the sample to be tested. In the reaction cartridge assembly of this example, each reaction unit 11 is provided with a first functional area, a second functional area, and a third functional area. The first functional area includes a cavity for sample injection, the second functional area includes cavities for extraction and purification, specifically including a cavity for sample lysis and fragmentation and a cavity for collecting biological macromolecules, and the third functional area includes a cavity for reaction detection; some cavities in the first functional area are internally connected to some cavities in the second functional area, or some cavities in the first functional area are respectively internally connected to some cavities in the second functional area and the third functional area; the cavity for collecting biological macromolecules in the second functional area is internally connected to the cavity for reaction detection in the third functional area. Specifically, as Figures 9 to 15 shown, the cavity for sample injection is an injection cavity 111, the second functional area is a nucleic acid extraction area 112, and the cavity for reaction detection is a detection reaction cavity 113.

[0096] Among them, the nucleic acid extraction area 112 is composed of an independently arranged lysis and fragmentation chamber 1121, a first rinsing chamber 1122, a second rinsing chamber 1123, and a collection chamber 1124 arranged in a circle; the lysis and fragmentation chamber 1121 is used to store cell lysis reagents and magnetic beads, that is, the chamber for sample lysis and fragmentation; the first rinsing chamber 1122 is used to store the reagents for the first rinsing, and the second rinsing chamber 1123 is used to store the reagents for the second rinsing. These two chambers are the chambers for rinsing; the collection chamber 1124 is used to store nucleic acid elution reagents, that is, the chamber for collecting biological macromolecules. The entire nucleic acid extraction area 112 is sealed by an extraction screw cap magnetic sleeve 1120. The extraction screw cap magnetic sleeve 1120, as Figure 16 and Figure 17 shown, at the positions corresponding to the lysis and fragmentation chamber 1121, the first rinsing chamber 1122, the second rinsing chamber 1123, and the collection chamber 1124, there are respectively provided sealing sleeves for closing each chamber; and, starting from the lysis and fragmentation chamber 1121, the extraction screw cap magnetic sleeve 1120 is provided with an electromagnetic column 1125 extending into the chamber at the corresponding position.

[0097] In this example, the entire nucleic acid extraction area 112 is arranged in a circular groove; the lysis and fragmentation chamber 1121, the first nucleic acid purification rinsing chamber 1122, the second nucleic acid purification rinsing chamber 1123, and the nucleic acid elution chamber 1124 are evenly arranged in the circular groove along the circumference of the circular groove; the extraction screw cap magnetic sleeve 1120 seals the entire circular groove, and, at the center of the circular groove, a protruding cylinder 1126 is provided, and the extraction screw cap magnetic sleeve 1120 rotates around the cylinder 1126, as Figure 11 and Figure 12 shown.

[0098] In the first functional area of this example, the chamber for sample injection is an injection chamber 111, which is used to place a quantitative sample to be tested, and the injection chamber 111 is connected to the lysis and fragmentation chamber 1121 of the nucleic acid extraction area 112 through a first pipeline 1111 arranged inside the reaction unit 11, as Figure 13 and Figure 14 shown.

[0099] As Figure 11 and Figure 12As shown, the sample injection chamber 111 in this example is equipped with a matching sample injection chamber sealer 1112. The upper part of the sample injection chamber 111 has internal threads; one end of the sample injection chamber sealer 1112 is an insertion part, and the insertion part is provided with external threads that match the internal threads of the sample injection chamber 111; the insertion part of the sample injection chamber sealer 1112 is extended into the sample injection chamber 111 through the operation of the robotic arm for tightening or opening, so as to realize the sealing and opening of the sample injection chamber 111; and, through the insertion of the insertion part, pressure is provided for the sample injection chamber 111 using the pressing principle, so that the sample to be tested therein enters the lysis and fragmentation chamber 1121. Among them, in this example, the position of the sample injection chamber is designed to be higher than that of the lysis and fragmentation chamber. The connecting pipe communicates the bottom of the sample injection chamber with the middle position of the lysis and fragmentation chamber, and, the bottom position of the sample injection chamber is higher than the connecting part of the lysis and fragmentation chamber, so that the entire connecting pipe, that is, the first pipe, has a downward-sloping structural design, which is more convenient for the entry of the sample.

[0100] In the third functional area of this example, the chamber for performing reaction detection is a detection reaction chamber 113, which is a tubular structure or a columnar chamber. In this example, it is specifically designed as a PCR tube structure. The lower part of the detection reaction chamber 113 is a transparent and smooth reaction area for placing nucleic acid detection reaction reagents; the upper part of the detection reaction chamber 113 is sealed by a matching reaction chamber sealer 1131; the middle part of the detection reaction chamber 113 is communicated with the bottom of the collection chamber 1124 in the nucleic acid extraction area 112 through a second pipe 1133 provided inside the reaction unit 11, as Figure 13 and Figure 14 shown. In the detection reaction chamber 113 of this example, the upper part of the chamber has internal threads, and the insertion end of the reaction chamber sealer 1131 has external threads that match it; when the reaction chamber sealer 1131 is inserted into the tubular structure chamber to seal it, the opening communicated with the collection chamber 1124 in the middle of the tubular structure chamber is also sealed.

[0101] In the improved solution of this example, the first functional area further includes a chamber for storing consumables and a chamber for placing sample tubes. The chamber for storing consumables is a consumable storage chamber 114, and the chamber for placing sample tubes is a sample tube storage chamber 115. The consumable storage chamber 114 in this example is a tip accommodating chamber, which is equipped with matching tips. The upper part of the tip accommodating chamber has internal threads, and the tips are provided with external threads that match it; after the tips are inserted into the tip accommodating chamber, the tips are fixed in the tip accommodating chamber by screwing tightly with the threads.

[0102] The sample tube storage cavity 115 in this example is used to place the sample tube containing the sample to be tested. The sample tube in this example is made of a highly permeable material, the tube body has protruding clamping positions, the upper part of the sample tube has internal threads, and the sample tube has a matching tube cap. The tube cap is threadedly connected to the sample tube and is tightened or opened by the operation of the robotic arm. Moreover, in the improved solution, a groove 116 and a hollow window 117 are provided on the arc-shaped side surface of the fan-shaped reaction unit 11; as Figure 12 shown, the hollow window 117 is arranged at the position of the sample tube storage cavity 115 to facilitate the observation or detection of the sample tube; the groove 116 is arranged side by side with the hollow window 117 and is used for pasting corresponding information or numbers.

[0103] The tray rack 13 in this example, as Figure 7 shown, has a frame structure and is surrounded on the circumference of the reaction unit tray 12, as Figure 8 shown; the tray rack 13 is movably connected to the reaction box assembly bracket 2, and the reaction box assembly 1 is installed on the reaction box assembly bracket 2. The reaction unit tray 12, as Figure 8 shown, is rotatably arranged in the tray rack 13 and is driven to rotate by a corresponding driving device. The surface of the reaction unit tray 12 in this example is provided with a number of cavities matching the reaction unit 11, as Figure 6 shown, for installing the reaction unit 11. Moreover, the center of the reaction unit tray 12 has a through-hole structure 122, and the detection reaction area 113 of the reaction unit 11 extends out of this through-hole and inserts into the cavity of the reaction detection module 4 for thermal reaction. In one implementation of this example, specifically, a rotary motor 121 is used for driving, and a belt 123 is used to drive the reaction unit tray 12, as Figures 3 to 5 shown; moreover, a gear structure is designed on the circumference of the reaction unit tray 12 to facilitate belt transmission.

[0104] The reaction detection module 4 in this example, as Figure 1 and Figure 2 shown, is arranged directly below the reaction box assembly 1, as Figure 2 shown. A cavity 41 corresponding to the tubular structure cavity of the detection reaction cavity 113 is provided on the reaction detection module 4 for providing thermal reaction for the detection reaction cavity 113.

[0105] The reaction box assembly bracket 2 in this example includes a vertical support body and a reaction box assembly driving device. The support body is used to support the entire reaction box assembly 1 in the vertical direction, and the reaction box assembly driving device is used to drive the reaction box assembly 1 to move up and down. Specifically in this example, as Figure 1 shown, the support body is composed of three vertical support columns, and the three support columns are evenly dispersed around the reaction box assembly 1.

[0106] The robotic arm 3 in this example, as Figure 1As shown, it is closely arranged beside the reaction cartridge assembly 1, used to achieve quantitative sample loading and the lifting and rotation operations of the extraction and capping magnetic sleeve 1120, and provide electrical energy for the electromagnetic column 1125. In one implementation of this example, specifically, the electrical connection of the electromagnetic column is achieved by the robotic arm contacting the extraction and capping magnetic sleeve, enabling it to adsorb magnetic beads.

[0107] In an improved solution of this example, on the back of the reaction unit 11, there are a lysis and fragmentation chamber 1121, a first rinsing chamber 1122, a second rinsing chamber 1123, and a collection chamber 1124. Each chamber has a protruding bottom, that is, on the back of the reaction unit 11, it is hollowed out at the position corresponding to the second functional area, so that each chamber in the second functional area forms a protruding independent tubular structure, as Figure 15 shown. An ultrasonic oscillator is installed on the outer wall of the protruding bottom. And the sample injection chamber 111, the first pipeline 1111, the collection chamber 1124, the second pipeline 1133, and the detection reaction chamber 113 are arranged on the central axis symmetry longitudinal section of the reaction unit 11, as Figure 13 and Figure 14 shown.

[0108] The key of this example lies in the design of the reaction cartridge assembly. In particular, the reaction unit is designed as a fan-shaped structure, and the reaction unit is divided into a first functional area, a second functional area, and a third functional area. Among them, the first functional area mainly includes chambers for sample injection, consumable storage, and sample tube storage, etc. The second functional area mainly includes chambers for nucleic acid or protein extraction and purification. The third functional area is mainly used for the detection reaction chamber. In this example, the three functional areas are designed to be isolated from each other, and are connected by internal pipelines, which not only realizes the automation of extraction and detection, but also maximally avoids various types of contamination.

[0109] It should be noted that the nucleic acid extraction and detection device with the above structure is only the internal structure for realizing the whole operation. As for the specific shell structure, it is only effectively enclosed into an integrated machine structure that is convenient to operate and beautiful. The shell structure can be designed according to requirements and is not specifically limited here. In addition, in order to realize real-time fluorescence PCR detection, the thermal reaction module of this example also includes a fluorescence collection device and a user terminal signal-connected thereto, and the real-time fluorescence PCR reaction results can be directly stored and viewed on the user terminal. The fluorescence collection component and the user terminal of the real-time fluorescence PCR can refer to the existing real-time fluorescence PCR instrument and are not specifically limited here.

[0110] The usage method of the device in this example is as follows:

[0111] a) In the reaction cell assembly of this example, the reaction units adopt a fan-shaped design. Multiple reaction units can be combined into a disc shape to achieve simultaneous detection of multiple samples. According to the specifications and the number of divisions of the disc, the number of samples can be adjusted, which has a certain degree of flexibility.

[0112] b) Each reaction unit contains an injection chamber, which is connected to the lysis and fragmentation chamber in the nucleic acid extraction area through an internal pipeline. The injection chamber has a threaded inner wall and is sealed by an injection chamber sealer, which is pre-tightened before the reaction cell is used to keep the internal environment clean.

[0113] c) Each reaction unit has a consumable storage chamber with a threaded inner wall, which is equipped with a special 1 mL pipette tip with a threaded outer wall. It is pre-tightened before use to keep the pipette tip clean. After the pipette tip is used, it is screwed back. Tightening by the thread can achieve the purpose of sealing and storing the contaminated consumables.

[0114] d) Each reaction unit has a sample tube storage chamber for storing the sample tubes after collection. The sample tubes are matching consumables, which are matched according to the pre-packaged detection items for detection. For example, if the sample type for the detection item is blood or serum, the corresponding vacuum blood collection tube is matched; if it is a plasma sample, the corresponding blood collection tube containing anticoagulant is matched; if it is feces, urine, sputum, etc., the sample tube containing diluent is matched; if it is tissue or other cell cultures, etc., the sample tube containing the corresponding buffer digestive solution is matched. The sample tubes or blood collection tubes are all made of highly permeable materials. The tube body has a protruding clamping position and a threaded inner wall, and the tube cap has a threaded outer wall, and can be tightened or opened by the operation of a robotic arm.

[0115] e) The lysis and fragmentation chamber can be pre-packaged with reagents such as lysis reagents, magnetic beads, and digestive enzymes according to different detection items. During the detection operation, the liquid sample in the injection chamber enters the lysis and fragmentation chamber through the extrusion of the injection chamber sealer, so that the pre-packaged lysis solution is fully mixed with the sample. An ultrasonic device is provided at the lower part of the reaction cell main body, which can lyse and fragment cells, microorganisms, etc. through the ultrasonic device, and at the same time achieve the effect of mixing.

[0116] f) The entire nucleic acid extraction area is sealed by an extraction screw-on magnetic sleeve. The extraction screw-on magnetic sleeve seals the nucleic acid extraction area through a rubber ring. Moreover, at the positions corresponding to the lysis and fragmentation chamber, the first rinsing chamber, the second rinsing chamber, and the collection chamber of the extraction screw-on magnetic sleeve, there are respectively provided sealing sleeves for closing each chamber. After the pre-sealed reagents are added, sealing preservation of the reagents can be achieved by pressing, and the screw-on magnetic sleeve is opened before use.

[0117] g) After the test sample is mixed with the lysis solution, the magnetic beads are adsorbed by the electromagnetic column of the extraction screw-cap magnetic sleeve, and the nucleic acid is adsorbed on the electromagnetic column together. The extraction screw-cap magnetic sleeve is lifted and rotated by the robotic arm to transfer the magnetic beads to the first rinsing chamber for the first rinse. After rinsing, adsorption is performed again, and then the magnetic beads are transferred to the second rinsing chamber for the second rinse; during the magnetic bead rinsing process, ultrasonic oscillation is used for mixing.

[0118] h) After the second rinse is completed, adsorption is performed again. Finally, the magnetic beads are transferred to the collection chamber for nucleic acid elution. Similarly, ultrasonic oscillation is used to fully elute the nucleic acid; after the elution is completed, the magnetic beads are adsorbed, and the nucleic acid is dissolved in the eluent.

[0119] Through the above steps a) to h), nucleic acid extraction and purification can be completed. Through the sample injection chamber, the consumable storage chamber, the sample tube storage chamber, and the supporting consumables, such as sample tubes or blood collection tubes, supporting pipette tips, sample injection chamber sealers, etc., automatic sample loading and transfer can be achieved, and closed nucleic acid extraction can be realized. Moreover, the problem of storing and handling consumables with sample residues is solved.

[0120] i) The detection reaction chamber is a tube-type structure cavity of a PCR tube. The lower part of the tube-type structure cavity is a transparent and smooth reaction area for placing nucleic acid detection reaction reagents; the upper part of the tube-type structure cavity is closed by an inserted cylindrical sealing structure, that is, the reaction chamber sealer, and a rubber ring is used for sealing; the middle part of the tube-type structure cavity is communicated with the bottom of the collection chamber in the nucleic acid extraction area through a pipeline arranged inside the reaction unit.

[0121] j) The detection reaction chamber contains pre-packaged reagents, which can be liquid or freeze-dried powder. In this example, it is specifically freeze-dried powder. When not in use, it is closed by the reaction chamber sealer and tightened by a thread for sealing. At the same time, the channel opening is closed, so that the eluent pre-packaged in the collection chamber cannot enter the detection reaction chamber in advance.

[0122] k) When the nucleic acid purification step is completed, that is, after the nucleic acid is eluted into the eluent, the robotic arm unscrews the reaction chamber sealer and simultaneously opens the connected pipeline port. Since the detection reaction chamber is sealed, a negative pressure is formed in the chamber, causing the nucleic acid solution in the collection chamber to enter the detection reaction chamber. The robotic arm tightens the cylindrical sealing structure again, and the sample loading step is completed.

[0123] l) After the conventional sample loading is completed, the reaction solution is mixed by ultrasonic oscillation. After mixing, the reaction cassette assembly bracket drives the entire reaction cassette assembly to move downward, so that the detection reaction chamber of the PCR tube structure of the reaction unit is inserted into the cavity of the reaction detection module, and the reaction detection module provides PCR or real-time fluorescence PCR reaction conditions for the reaction. For real-time fluorescence PCR, the reaction detection module also includes a fluorescence collection component and a user terminal signal-connected thereto, such as a computer, and the real-time fluorescence PCR detection result can be directly obtained on the user terminal.

[0124] Through steps i) to l), the technical solution for automatic nucleic acid sample addition and detection reaction is completed. The device in this example can achieve full-automatic nucleic acid sample addition in a closed state and closed nucleic acid detection through the negative pressure effect of the detection reaction chamber, solving the defects and deficiencies existing in manual transfer of reaction tubes. While reducing the use of consumables, it improves the accuracy of liquid addition to the reaction system.

[0125] The device in this example adopts designs such as mechanical and pipette-in-tube, is not limited by the sample type and sample volume, has no liquid residue in the overall detection reaction, and does not require multi-channel air pumps or pushing devices. When in use, only a fixed robotic arm with the ability of Z-axis displacement needs to be configured. By rotating the disc-shaped reaction unit tray, multiple samples can be operated for detection simultaneously.

[0126] It should be noted that this example specifically provides a device for nucleic acid extraction and detection. It can be understood that the structures of devices for protein or hormone extraction and detection are similar to this example, and also include a reaction cartridge assembly and a detection system. Similarly, the reaction cartridge assembly includes several fan-shaped reaction units, and the reaction units are provided with a first functional area, a second functional area, and a third functional area. The difference is that the specific functional cavities and their numbers set in the first functional area, the second functional area, and the third functional area are different. Especially for the second functional area, for nucleic acid extraction, two rinsing cavities, namely a first rinsing cavity and a second rinsing cavity, need to be set. However, for protein extraction, there is no need for rinsing cavities, and only a lysis and fragmentation cavity and a collection cavity are required. The designs of the first functional area and the third functional area refer to the nucleic acid extraction and detection device in this example. In addition, in terms of the detection system, this example refers to a PCR instrument, and for proteins or hormones, corresponding existing detection systems can be referred to. The rest of the structures are similar to the nucleic acid extraction and detection device in this example.

[0127] The above content is a further detailed description of the present application in combination with specific implementation manners, and it cannot be determined that the specific implementation of the present application is only limited to these descriptions. For those of ordinary skill in the technical field to which the present application belongs, without departing from the concept of the present application, several simple deductions or substitutions can still be made.

Claims

1. A device for the extraction and detection of biological macromolecules, wherein the biological macromolecules are proteins, hormones or nucleic acids, and is characterized in that: It includes a reaction cartridge assembly (1) and a detection system; The reaction cartridge assembly (1) includes a number of fan-shaped reaction units (11), and all the reaction units are assembled into a disc-shaped reaction cartridge. Each reaction unit (11) is used to independently extract and detect biological macromolecules in the sample to be tested; Each reaction unit (11) is provided with a first functional area, a second functional area and a third functional area. The first functional area includes a cavity for sample injection, the second functional area includes a cavity for extraction and purification, and the third functional area includes a cavity for reaction detection; Some cavities in the first functional area are internally connected to some cavities in the second functional area; Some cavities in the second functional area are internally connected to the cavities in the third functional area for reaction detection; The detection system is used to control the reaction cartridge assembly (1) to extract and detect biological macromolecules; The second functional area is arranged at the central position of the fan-shaped reaction unit, and all the cavities in the second functional area are evenly arranged on a circumference centered on the central position; The cavities in the first functional area are arranged on the arc of the fan-shaped reaction unit.

2. The device according to claim 1, wherein: The entire second functional area is arranged in a circular groove centered on the central position, and the circular groove is closed by an extraction rotary cover magnetic sleeve (1120), so as to seal the second functional area in the circular groove.

3. The device according to claim 2, characterized in that: At the positions corresponding to each cavity, the extraction rotary cover magnetic sleeve (1120) is respectively provided with a sealing sleeve for closing each cavity, and the extraction rotary cover magnetic sleeve (1120) is provided with an electromagnetic column (1125) extending into the cavity.

4. The device according to claim 3, characterized in that: In the second functional area, the cavities for extraction and purification include a cavity for lysis and fragmentation and a cavity for collecting biological macromolecules.

5. The device according to claim 4, wherein: The second functional area also includes a cavity for rinsing.

6. The device according to claim 5, characterized in that: The cavity for lysis and fragmentation is at least one lysis and fragmentation cavity (1121), the cavity for collecting biological macromolecules is at least one collection cavity (1124), and the cavities for rinsing include a first rinsing cavity (1122) and a second rinsing cavity (1123); the cavities in the second functional area are independently arranged, and the cavity for sample injection in the first functional area is internally connected to the lysis and fragmentation cavity (1121), and the cavity for reaction detection in the third functional area is internally connected to the collection cavity (1124).

7. The device according to claim 6, characterized in that: At the positions corresponding to the lysis and fragmentation cavity (1121), the first rinsing cavity (1122), the second rinsing cavity (1123) and the collection cavity (1124), the extraction rotary cover magnetic sleeve (1120) is respectively provided with a sealing sleeve for closing each cavity; and starting from the lysis and fragmentation cavity (1121), the extraction rotary cover magnetic sleeve (1120) is provided with an electromagnetic column (1125) extending into the cavity at the corresponding position.

8. The device according to claim 1, characterized in that: On the back of the reaction unit (11), at the position corresponding to the second functional area, it is a hollow structure, so that the cavities in the second functional area are in a protruding independent tubular structure, and an oscillator is connected to the outer wall of each protruding cavity.

9. The device according to claim 8, wherein: The connecting pipes between the first functional area and the second functional area, the connecting pipes between the second functional area and the third functional area, the cavity in the first functional area for sample injection, the cavity in the second functional area for sample lysis and fragmentation, and the cavity in the third functional area for reaction detection are all arranged on the central axis symmetric longitudinal section of the reaction unit (11).

10. The device according to claim 1, characterized in that: In the first functional area, the cavity for sample injection is at least one sample injection cavity (111). The sample injection cavity (111) is internally connected to the second functional area to provide the sample to be tested for the second functional area.

11. The device according to claim 10, wherein: The sample injection cavity (111) is equipped with a supporting sample injection cavity sealer (1112). The two are in an insert - type sealing fit and are connected by threads. Moreover, by inserting the sample injection cavity sealer (1112) into the sample injection cavity (111), pressure is provided for the sample injection cavity (111) using the pushing principle, so that the sample to be tested therein enters the second functional area for extraction and purification.

12. The device according to claim 11, wherein: The first functional area also includes a cavity for storing consumables.

13. The device according to claim 12, wherein: The cavity for storing consumables is at least one consumable storage cavity (114). The consumable storage cavity (114) is a pipette tip accommodating cavity, which is equipped with a matching pipette tip. The pipette tip and the pipette tip accommodating cavity are in an insert - type tight fit and are fixed by thread connection.

14. The device according to claim 11, characterized in that: The first functional area also includes a cavity for placing sample tubes.

15. The device according to claim 14, characterized in that: The cavity for placing sample tubes is at least one sample tube storage cavity (115) for placing sample tubes containing the sample to be tested.

16. The device according to claim 15, characterized in that: The sample tube is made of a highly permeable material. The tube body contains protruding clamping positions. The upper part of the sample tube contains threads. The sample tube is equipped with a supporting tube cap, and the tube cap is thread - connected to the sample tube.

17. The device according to claim 16, characterized in that: On the arc - shaped side surface of the fan - shaped reaction unit (11), there is a groove (116) and a hollowed - out viewing window (117). The hollowed - out viewing window (117) is arranged at the position of the sample tube storage cavity (115) to facilitate observing or detecting the sample tube. The groove (116) is arranged side - by - side with the hollowed - out viewing window (117) for pasting corresponding information or numbers.

18. The device according to claim 1, characterized in that: The cavity of the third functional area is arranged at the included angle of the fan - shaped reaction unit. Moreover, in the disc - shaped reaction box, the cavities for reaction detection of all reaction units are evenly distributed on the circumference of the center of the fan - shaped reaction unit.

19. The device according to claim 18, characterized in that: In the third functional area, the cavity for reaction detection is at least one detection reaction cavity (113). The detection reaction cavity (113) is internally connected to the second functional area to receive the biological macromolecules extracted and purified by the second functional area.

20. The device according to claim 19, characterized in that: The detection reaction cavity (113) is a tubular structure or a columnar cavity. The lower part of the detection reaction cavity (113) is a transparent and smooth reaction area for placing detection reaction reagents. The upper part of the detection reaction cavity (113) is sealed by a supporting reaction cavity sealer (1131).

21. The device according to claim 20, wherein: The reaction cavity sealer (1131) and the detection reaction cavity (113) are in an insert - type sealing fit and are connected by threads. When the reaction cavity sealer (1131) is inserted into the detection reaction cavity (113) to seal it, the opening connecting the detection reaction cavity (113) and the second functional area is also closed.

22. The device according to any one of claims 1-21, characterized in that: The detection system includes a reaction cassette assembly support (2), a robotic arm (3), and a reaction detection module (4). The reaction cassette assembly support (2) includes a vertical support body and a reaction cassette assembly driving device. The support body is used to support the reaction cassette assembly (1) as a whole in the vertical or horizontal direction, and the reaction cassette assembly driving device is used to drive the reaction cassette assembly (1) to move up and down or horizontally. The reaction detection module (4) is arranged directly below the reaction cassette assembly (1). A cavity matching the cavity for reaction detection in the third functional area is provided on the reaction detection module (4), which is used to provide corresponding reaction and detection conditions for the reaction detection cavity. The robotic arm (3) is arranged adjacent to the reaction cassette assembly (1) and is used for sample addition and performing clamping, up and down movement, and rotation operations.

23. The device according to claim 22, characterized in that: The detection system further includes an information reading module, which is used to detect and read the information of the sample and the reaction unit.

24. The device according to claim 22, characterized in that: The reaction cassette assembly (1) further includes a disc-shaped reaction unit tray (12) and a tray holder (13). The tray holder (13) is a frame structure that surrounds the circumference of the reaction unit tray (12). The tray holder (13) is movably connected to the reaction cassette assembly support (2) to mount the reaction cassette assembly (1) on the reaction cassette assembly support (2). The reaction unit tray (12) is rotatably arranged in the tray holder (13) and is driven to rotate by a corresponding driving device. A number of cavities matching the reaction units (11) are provided on the surface of the reaction unit tray (12) for mounting the reaction units (11). Moreover, a through-hole structure is provided at the center of the reaction unit tray (12). The cavity for reaction detection in the third functional area of the reaction unit (11) extends out of the through-hole and inserts into the cavity of the reaction detection module (4) for reaction.

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